Association of Phenylacetylglutamine and Cognitive Impairment in CKD

Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs). Studies have suggested that UTs are associated with cognitive impairment (CI) in patients with CKD. Recently, studies reported that phenylacetylglutamine (PAG) contributes to the association between CKD and CI. However, this association has not been investigated in nondialysis-dependent adults with CKD.

The CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort study included 3033 patients with CKD stages 2 to 5. This cross-sectional analysis included those with a PAG measurement and a mini-mental state examination (MMSE) score within 3 months of each other. CI was defined as an MMSE score ≤ 26 out of 30. Logistic regression was used to assess the association between PAG and CI.

Of the 2590 patients included (mean [SD] age: 67 [13] years, mean [SD] estimated glomerular filtration rate [eGFR]: 34 [13] ml/min per 1.73 m², median [interquartile range, IQR] PAG level: 2.1 [1.2-3.6] mg/l), 908 (35%) presented an MMSE score ≤ 26 out of 30. After adjustment for sociodemographic factors (age, male sex, and educational level), cardiovascular risk factors, cerebrovascular disease, current depression, eGFR, urinary albumin-to-creatinine ratio (uACR), and UTs known to be associated with CI risk, a 2-fold increase in the PAG level was associated with CI (odds ratio [OR] [95% confidence interval]: 1.12 [1.01-1.23]).

This study shows that a higher serum PAG level was associated with CI in nondialysis-dependent adults with CKD and highlight a new UT associated with CI in patients with CKD. Further studies are needed to confirm the causal nature of the association and to explore strategies for reducing serum PAG levels to protect cognition.